The overall aim is to develop a practical means of purification of human beta-glucuronidase for enzyme therapy for deficient human subjects and to extend the approaches developed with this model to other lysosomal enzyme deficiencies: 1) Human beta-glucuronidase will be purified from several sources to provide highly purified enzyme for analytical studies, and to determine the best practical source and purification scheme for enzyme replacement. Immunoadsorbant columns will be emphasized in purification and cultured fibroblasts used to guide purification for the enzyme form with high uptake and corrective activity. 2) An animal model system will be developed to study the uptake, distribution and fate of radiolabelled human beta-glucuronidase infused into the whole animal. 3) The clinical response of beta-glucuronidase deficient patients to infusion of purified human beta-glucuronidase with high in vitro corrective activity will be studied. 4) The methods developed from the enzyme purification and the cell culture and animal studies will be applied to other lysosomal enzyme deficiencies.